Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors

Childhood Cancer Survivor Study

Authors


  • The following are Childhood Cancer Survivor Study (CCSS) institutions and investigators: University of California-San Francisco, CA (Arthur Ablin, M.D., Institutional Principal Investigator); University of Alabama, Birmingham, AL (Roger Berkow, M.D., Institutional Principal Investigator); International Epidemiology Institute, Rockville, MD (John Boice, Sc.D., member CCSS Steering Committee); University of Washington, Seattle, WA (Norman Breslow, Ph.D., member CCSS Steering Committee); University of Texas Southwestern Medical Center at Dallas, TX (George R. Buchanan, M.D., Institutional Principal Investigator); Dana-Farber Cancer Institute, Boston, MA (Lisa Diller, M.D., Institutional Principal Investigator; Holcombe Grier, M.D., former Institutional Principal Investigator; Frederick Li, M.D., member CCSS Steering Committee); Texas Children's Center, Houston, TX (Zoann Dreyer, M.D., Institutional Principal Investigator); Seattle Children's Hospital, Seattle, WA (Debra Friedman, M.D., M.P.H., Institutional Principal Investigator; Thomas Pendergrass, M.D., former Institutional Principal Investigator); Roswell Park Cancer Institute, Buffalo, NY (Daniel M. Green, M.D., Institutional Principal Investigator and member CCSS Steering Committee); Hospital for Sick Children, Toronto, ON (Mark Greenberg, M.B., Ch.B., Institutional Principal Investigator); St. Louis Children's Hospital, MO (Robert Hayashi, M.D., Institutional Principal Investigator; Teresa Vietti, M.D., former Institutional Principal Investigator); St. Jude Children's Research Hospital, Memphis, TN (Melissa Hudson, M.D., Institutional Principal Investigator and member CCSS Steering Committee); University of Michigan, Ann Arbor, MI (Raymond Hutchinson, M.D., Institutional Principal Investigator); Stanford University School of Medicine, Stanford, CA (Michael P. Link, M.D., Institutional Principal Investigator; Sarah S. Donaldson, M.D., member CCSS Steering Committee); Children's Hospital of Philadelphia, PA (Anna Meadows, M.D., Institutional Principal Investigator and member CCSS Steering Committee; Bobbie Bayton, member CCSS Steering Committee); Children's Hospital, Oklahoma City, OK (John Mulvihill, M.D., member CCSS Steering Committee); Children's Hospital, Denver, CO (Brian Greffe, M.D., Institutional Principal Investigator; Lorrie Odom, M.D., former Institutional Principal Investigator); Children's Health Care-Minneapolis, MN (Maura O'Leary, M.D., Institutional Principal Investigator); Columbus Children's Hospital, OH (Amanda Termuhlen, M.D., Institutional Principal Investigator; Frederick Ruymann, M.D., former Institutional Principal Investigator; Stephen Qualman, M.D., member CCSS Steering Committee); Children's National Medical Center, Washington, DC (Gregory Reaman, M.D., Institutional Principal Investigator; Roger Packer, M.D., member CCSS Steering Committee); Children's Hospital of Pittsburgh, PA (A. Kim Ritchey, M.D., Institutional Principal Investigator; Julie Blatt, M.D., former Institutional Principal Investigator); University of Minnesota, Minneapolis, MN (Leslie L. Robison, Ph.D., Institutional Principal Investigator and member CCSS Steering Committee; Ann Mertens, Ph.D., member CCSS Steering Committee; Joseph Neglia, M.D., M.P.H., member CCSS Steering Committee; Mark Nesbit, M.D., member CCSS Steering Committee; Stella Davies, M.D., Ph.D., member CCSS Steering Committee); Children's Hospital Los Angeles, CA (Kathy Ruccione, R.N., M.P.H., Institutional Principal Investigator); Memorial Sloan-Kettering Cancer Center, New York, NY (Charles Sklar, M.D., Institutional Principal Investigator and member CCSS Steering Committee); National Cancer Institute, Bethesda, MD (Malcolm Smith, M.D., member CCSS Steering Committee; Martha Linet, M.D., member CCSS Steering Committee); Mayo Clinic, Rochester, MN (W. Anthony Smithson, M.D., Institutional Principal Investigator; Gerald Gilchrist, M.D., former Institutional Principal Investigator); University of Texas M. D. Anderson Cancer Center, Houston, TX (Louise Strong, M.D., Institutional Principal Investigator and member CCSS Steering Committee; Marilyn Stovall, Ph.D., member CCSS Steering Committee); Riley Hospital for Children, Indianapolis, IN (Terry A. Vik, M.D., Institutional Principal Investigator; Robert Weetman, M.D., former Institutional Principal Investigator); Fred Hutchinson Cancer Center, Seattle, WA (Yutaka Yasui, Ph.D., Institutional Principal Investigator; John Potter, M.D., Ph.D., former Institutional Principal Investigator and member CCSS Steering Committee); and University of California-Los Angeles, CA (Lonnie Zeltzer, M.D., Institutional Principal Investigator and member CCSS Steering Committee)

Abstract

BACKGROUND

Survivors of childhood brain tumors (CBTs) are at high risk for a variety of late adverse effects. Most research on long-term effects of CBTs has been comprised of single-institution case series without comparison groups. Research on CBT late effects often is focused on neurologic and sensory outcomes, with less emphasis on other potential targets such as the endocrine and circulatory systems. The current study was conducted to contrast the incidence of endocrine and cardiovascular conditions among CBT survivors as a function of treatment and to determine the risk of occurrence of these conditions relative to a sibling comparison group.

METHODS

As part of the Childhood Cancer Survivor Study (CCSS), treatment data were collected from medical records and self-reported late effects were ascertained from a survey questionnaire of 1607 CBT patients who survived their disease for 5 or more years. For comparison purposes, questionnaire data were also collected from 3418 randomly selected siblings of participants in CCSS.

RESULTS

One or more endocrine conditions were reported by 43% of CBT survivors. Compared with siblings, CBT survivors had a significantly increased risk of late-onset (≥ 5 years postdiagnosis) hypothyroidism (relative risk [RR] = 14.3; 95% confidence interval [95% CI] 9.7–21.0), growth hormone deficiency (RR = 277.8; 95% CI 111.1–694.9), the need for medications to induce puberty (RR = 86.1; 95% CI 31.1–238.2), and osteoporosis (RR = 24.7; 95% CI 9.9–61.4). One or more cardiovascular conditions were reported by 18% of CBT survivors, with an elevated late-onset risk for stroke (RR = 42.8; 95% CI 16.7–109.8), blood clots (RR = 5.7; 95% CI 3.2–10.0), and angina-like symptoms (RR = 2.0; 95% CI 1.5–2.7). Very few late effects were evident among those treated with surgery only, but risks were consistently elevated for those treated with radiation and surgery, and higher still for those who also received adjuvant chemotherapy.

CONCLUSIONS

Childhood brain tumor survivors are at a significantly increased risk for several adverse endocrine and cardiovascular late effects, particularly if they were treated with radiation and chemotherapy. Lifetime medical surveillance and follow-up for potential toxicities are necessary because treatment-related complications may occur many years after therapy. Cancer 2003;97:663–73. © 2003 American Cancer Society.

DOI 10.1002/cncr.11095

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